Expression of prostate‐specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non‐polyglutamated folate, folic acid

@article{Yao2010ExpressionOP,
  title={Expression of prostate‐specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non‐polyglutamated folate, folic acid},
  author={V. Yao and C. Berkman and Joseph K. Choi and D. O’Keefe and D. Bacich},
  journal={The Prostate},
  year={2010},
  volume={70}
}
Prostate specific membrane antigen (PSMA) is a unique folate hydrolase that is significantly upregulated in prostate cancer. In a mouse model, PSMA is able to facilitate prostate carcinogenesis, however, little is known about the mechanism by which this occurs. As PSMA is able to hydrolyze polyglutamated folates, and cancer cells proliferate directly in response to available folate, we examined if expression of human PSMA in PC‐3 cells confers a proliferative advantage in a microenvironment… Expand
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TLDR
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TLDR
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References

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Prostate specific membrane antigen (PSMA) expression gives prostate cancer cells a growth advantage in a physiologically relevant folate environment in vitro
TLDR
This work studied if PSMA folate hydrolase activity provides cells a growth advantage in a low folate (LF) micro‐environment by hydrolyzing extracellular poly‐γ‐glutamated folate to a form that cells can import. Expand
Prostate‐specific membrane antigen (PSMA) enzyme activity is elevated in prostate cancer cells
TLDR
The prostate enzyme has activity in both the membrane and cytosolic fractions termed PSMA and PSMA′, respectively. Expand
Moderate expression of prostate-specific membrane antigen, a tissue differentiation antigen and folate hydrolase, facilitates prostate carcinogenesis.
TLDR
The results suggest PSMA facilitates the development of prostate cancer, and the invasive ability of these cells may be modulated by folate levels, a novel mechanism that may contribute to the known role of folate in cancer prevention. Expand
Novel role of prostate-specific membrane antigen in suppressing prostate cancer invasiveness.
TLDR
In vitro invasion assays are used to explore the possible role of PSMA in the metastasis of prostate cancer cells and it seems that the enzymatic activity is associated with the effect of PSma on invasiveness. Expand
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  • Biology, Medicine
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TLDR
It is demonstrated clearly that LNCaP cells, which highly express PSM, hydrolyze gamma-glutamyl linkages of MTXGlu3 and pteroylpentaglutamate as substrates and that cancer cells that express this enzyme are resistant to methotrexate therapy. Expand
Use of Methotrexate-Based Peptide Substrates to Characterize the Substrate Specificity of Prostate-Specific Membrane Antigen (PSMA)
TLDR
These studies have identified PSMA selective, plasma stable peptide substrates that can be incorporated into prodrugs targeted for activation by PSMA within prostate cancer sites. Expand
Characterization of the enzymatic activity of PSM: Comparison with brain NAALADase
TLDR
The NAAG hydrolyzing activity of NAALADase and the prostate enzyme PSM is compared to find out whether this enzyme cleaves terminal carboxy glutamates from both the neuronal peptide N‐acetylaspartyl glutamate (NAAG) and folate polyglutamate. Expand
Prostate-Specific Membrane Antigen Regulates Angiogenesis by Modulating Integrin Signal Transduction
TLDR
A novel role is identified for PSMA as a true molecular interface, integrating both extracellular and intracellular signals during angiogenesis, and it is shown that PSMA participates in an autoregulatory loop, wherein active PSMA facilitates integrin signaling and PAK activation, leading to both productive invasion and downregulation of integrin β1 signaling. Expand
Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy.
TLDR
The enhanced expression of PSMA in tissues and LNCaP cells after androgen deprivation suggests that PSMA is upregulated in the majority of prostate carcinomas after androgens treatment, and suggests thatPSMA may be a clinically useful target for antibody-and genetic-directed therapy of prostate cancer that recurs after androd deprivation. Expand
A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen.
TLDR
It is suggested that a novel MXXXL motif in the cytoplasmic tail mediates PSMA internalization, and it is shown that dominant negative micro2 of the adaptor protein (AP)-2 complex strongly inhibits the internalization of PSMA, indicating that AP-2 is involved in the internalized of PSma mediated by the M XXXL motif. Expand
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